Analysis Tools
mortality/aging
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• some die at weaning unless wet feed is provided
• delaying weaning by 1 week also greatly improves survival
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• some homozygotes that experience severe seizures die
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growth/size/body
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• 15% smaller at weaning and at 12 weeks of age
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• apparent after 2 weeks of age
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• the lag phase in the growth of wild-type mice between 2 and 3 weeks of age coincides with a period of weight loss in homozygotes and the growth spurt immediately after the lag phase is delayed by 1 week and is not as robust as in wild-type
• growth of homozygotes is much slower during the 4th week and marginally, but significantly, faster during weeks 5 and 6 and catches up with wild-type after that time, however homozygotes are still smaller than wild-type due to the extra weight gained by wild type during the early growth spurt that does not occur in mutants
• growth is improved if homozygotes are fed a high protein diet
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• kidney weight is increased by about 10%
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• liver weight is increased by about 10%
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behavior/neurological
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• exhibit hind limb flexion, extension, and clinching of the hind limbs to their body when hung by the tail
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• starting at 3 weeks of age, exhibit an abnormal gait with a predilection to splay their hind limbs
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• at approximately 6-7 months of age, develop epileptic seizures, lasting for a few seconds to as long as 2 min
• seizures can be evoked by touching, gently hanging the mutant by the tail for a few seconds or cage changing
• seizure activity starts with lip smaking followed by head bobbing and frequently progresses to fore limb clonus, rearing and generalized tonic/clonic seizure activity with foaming in the mouth
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• seizure activity frequently progresses to generalized tonic-clonic seizures
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homeostasis/metabolism
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• branched-chain amino acid levels are 70-75%, 55%, 50%, and 70% lower in the brain, heart, muscle, and kidney, respectively
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• branched-chain amino acid levels are 50-60% lower than in wild-type
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• diaphragms oxidize valine to CO2 at 3 times the rate seen in wild-type, resulting in increased CO2 production
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adipose tissue
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• adipose tissue weight is 40% less than in wild-type
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liver/biliary system
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• liver weight is increased by about 10%
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muscle
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• muscle weight is 15% less than in wild-type
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renal/urinary system
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• kidney weight is increased by about 10%
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reproductive system
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• although litters are obtained within a month of setting up mating pairs, 3 of the breeding pairs required 8 weeks to produce litters and 6 of the breeding pairs failed to reproduce
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nervous system
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• at approximately 6-7 months of age, develop epileptic seizures, lasting for a few seconds to as long as 2 min
• seizures can be evoked by touching, gently hanging the mutant by the tail for a few seconds or cage changing
• seizure activity starts with lip smaking followed by head bobbing and frequently progresses to fore limb clonus, rearing and generalized tonic/clonic seizure activity with foaming in the mouth
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• seizure activity frequently progresses to generalized tonic-clonic seizures
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• brain weight is 30% less than in wild-type
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integument
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• fur lacks normal luster at 12 weeks of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| branched-chain keto acid dehydrogenase kinase deficiency | DOID:0090126 |
OMIM:614923 |
J:187971 | |
